Bia 1981
Bia 1981
Bia 1981
'Assistant Professor of Medicine; Assistant Director, Dialysis and Transplant Program, Yale
University School of Medicine, New Haven, Connecticut
tDavid Paige Smith Professor of Medicine; Chairman, Department of Medicine, Yale University
School of Medicine, New Haven, Connecticut
Medical Clinics of North America - Vo!. 65, No. 2, March 1981 347
348 MARGARET BIA AND SAMUEL O. THIER
compromise and initiate appropriate treatment to lower the Pco 2 and compen-
sate for the metabolic acidosis. Identification of mixed disturbances has other
important therapeutic implications as well. Patients with chronic respiratory
acidosis due to severe pulmonary disease often have a coexisting metabolic
alkalosis secondary to the aggressive use of diuretics to treat congestive heart
failure. a7 Failure to appreciate and therefore treat the alkalosis, particularly
when the patients are on respirators, can add to the respiratory depression a
and can create difficulty in weaning such patients from ventilatory support.
Thus it should be clear that an understanding of complex acid-base disturb-
ances provides the clinician with an important diagnostic skill that can be
utilized to provide better evaluation and management.
INTRODUCTORY CONCEPTS
HCOa
pH = pK log .03 X PC02 (1)
LIMITS OF COMPENSATION
Metabolic alkalosis Each mEq t in HC0 3 --> 0.5-1.0 mmHg t in PCO, 55 mmHg
Chronic respiratory Each mmHg t in PCO, --> 0.4 mEq/L t in HCO, 45 mEq/L
acidosis
Chronic respiratory Each mmHg t in PCO, -->0.5 mEq/L t in HC0 3 12-15 mEq/L
alkalosis
350 MARGARET BIA AND SAMUEL O. THIER
Dr. McCurdy, to whom this issue is dedicated, was noted for her teaching
of acid-base physiology. One of her greatest contributions to the subject was
the development of a systematic method for analyzing acid-base disorders
352 MARGARET BIA AND SAMUEL O. THIER
using a clinical approach. 28 The essential steps involved in this method are
outlined in Table 2. Basically, information from the clinical history, the
physical examination and the laboratory data are all utilized to identify an
acid-base disorder{s).
The first step in this approach is a careful history searching for clues that
lead the clinician to suspect the presence of certain acid-base disturbances.
Major causes for the simple acid-base disorders should be kept in mind so that
a disorder can be predicted by the presence of certain disease states. Thus, a
patient with chronic renal failure would be expected to have a metabolic
acidosis, while in a patient with a history of vomiting, a metabolic alkalosis
would be the predicted disorder. Acid-base disorders that are common in
certain clinical settings should also be remembered, such as respiratory
alkalosis in patients with pneumonia, sepsis or congestive heart failure, and
lactic acidosis in patients with septic shock. The ingestion of certain drugs
should alert the clinician to potential disturbances such as metabolic alkalosis
in a patient taking a loop-acting diuretic or metabolic acidosis in a subject
taking acetazolamide.
Additional clues to a possible acid-base disorder{s) can be obtained
during physical examination. For example, in a patient with clinical signs of
extracellular fluid volume contraction, a metabolic alkalosis should be sus-
pected. Similarly, tetany may be a manifestation of alkalemia; cyanosis may
reflect respiratory failure and therefore respiratory acidosis; fever is often
associated with respiratory alkalosis, etc. Thus, there are many signs on
physical examination which can lead the clinician to expect an acid-base
disturbance. This possibility is then either supported or excluded by an
evaluation of the laboratory data. Routine non-electrolyte chemistries are
useful in predicting disturbances. An elevated serum creatinine concentration
indicating renal failure makes a metabolic acidosis . likely. An increase in
serum glucose concentration with positive serum ketones suggests diabetic
ketoacidosis. Serum electrolytes provide further evidence for a possible
acid-base disorder.
When examining the serum electrolytes for signs of an acid-base disturb-
ance, four steps should be taken. First, the serum HC0 3 concentration should
be noted. Any deviation in serum HC0 3 from normal has one of two
TREATMENT
patient with a serum HCO a- of 11 mEq/L and a pH of 7.20 but should not be
given to a patient with a serum HCO a- of 11 mEq/L but with a normal pH of
7.40 because of a concomitant primary respiratory alkalosis. This is not to
imply that the acid-base disturbances in the second patient is less severe than
in the first patient but only to emphasize that the need for specific therapy
depends on the blood pH. Second, in treating combined disorders, the effect
of treatment of one disturbance on the manifestation of the second disorder
should be anticipated. For example, in a patient with a chronic respiratory
acidosis plus a metabolic alkalosis, improving ventilation to lower Pco 2
without simultaneously treating the alkalosis to lower HCO a- can'leave the
patient with a significant alkalemia. Thus the goal of therapy in mixed
disorders is to treat the blood pH, always being aware of the effect of such
therapy on all of the disturbances present.
While there are a large number of possible combinations, a few mixed
disturbances deserve special mention because of their clinical importance;
these are listed in Table 3. No attempt has been made to review all mixed
disturbances but rather to describe the ones that are most likely to be
encountered clinically and are important because of their diagnostic and
therapeutic implications.
Respiratory Acidosis Plus Metabolic Acidosis
This combination occurs in a variety of clinical situations including
cardiopulmonary arrest, severe pulmonary edema, drug ingestion with severe
central nervous system depression and hypoventilation, and metabolic acido-
sis with potassium depletion producing paralysis of the respiratory muscles.
In these cases, the serum bicarbonate is usually low, the Pco 2 normal or
MIXED ACID BASE DISTURBANCES 357
elevated, and the resultant pH may be dangerously low. The CO 2 retention
prevents respiratory compensation for the metabolic acidosis and the meta-
bolic process prevents compensation for the respiratory acidosis. Significant
acidemia can seriously impair cardiac function and lead to cardiovascular
collapse. 3o Specific therapy must be initiated aggressively to correct the
acidemia by simultaneously treating the metabolic acidosis with bicarbonate
and the respiratory acidosis with measures to improve ventilation. Frequently
intubation is required in these situations, a fact which may be obvious when
the Pco 2 is 60 mm Hg but may not be so easy to appreciate if the Pco 2 is not
elevated much above 40 mm Hg. However, as discussed earlier, a normal
Pco 2 in the setting of a severe metabolic acidosis may be as strong evidence of
respiratory acidosis as is a Pco 2 of 60 mm Hg in a patient without a metabolic
acidosis. The clinician should also be aware that the sodium bicarbonate
therapy for the metabolic acidosis may cause excessive volume expansion and
further compromise ventilation. Rules for calculating the amount ofbicarbon-
ate necessary are described by Drs. Gardner and Narins. A final point to
remember regarding treatment for a mixed respiratory and metabolic acidosis
is that hyperkalemia is frequently a serious problem in this setting requiring
aggressive therapy both to shift potassium intracellularly and to remove it
from the body.
Respiratory Alkalosis Plus Metabolic Alkalosis
This mixed disorder is commonly present in patients with hepatic failure
who are placed on diuretics or nasogastric suction. It is also common in
critically ill patients who require ventilator support and are given diuretics or
nasogastric suction. 43 In these cases, the serum HC03 - is usually elevated, the
Pco 2 is normal or low and the blood pH is, of course, alkaline. This disorder
deserves special mention because the profound alkalemia which may result
demands immediate specific therapy. Severe alkalemia can adversely affect
both cerebral and peripheral hemodynamics. 4 , 24, 30 and is associated with a
poor prognosis in critically ill patients. 43 In this mixed disturbance, the
metabolic process prevents compensation for the respiratory alkalosis and the
hyperventilation prevents compensation for the metabolic alkalosis. In order
to return the pH toward normal, therapy theoretically should again be
directed at alleviating both disorders simultaneously. Treatment of the
metabolic alkalosis with volume, chloride and potassium replacement should
be initiated. If the patient is on a ventilator, the settings should be adjusted to
increase the Pco 2 • However, raising the Pco 2 is more difficult in a patient
with spontaneous hyperventilation unless the underlying process leading to
the increased respiratory drive can be corrected. In these cases, the clinician
should accept the presence of the respiratory alkalosis and concentrate efforts
on reversing the metabolic process. Potassium deficits in this setting may be
significant and replacement with large amounts of the cation should be an-
ticipated.
Respiratory Alkalosis Plus Metabolic Acidosis
Clinical settings in which this combination can be found include septic
shock, pulmonary embolism, renal failure with sepsis and salicylate ingestion.
The metabolic acidosis in these cases is frequently of the anion gap variety
358 MARGARET BIA AND SAMUEL O. THIER
SUMMARY
The analysis of a mixed acid-base disturbance begins with the history and
physical examination from which data can be derived that make the clinician
suspect a specific disturbance(s). The electrolytes are then evaluated with
emphasis on the meaning of the values for serum bicarbonate, potassium and
chloride concentration and on the level of the anion gap. Other laboratory data
such as serum creatinine or glucose concentrations, blood cultures, and so
forth, should also be reviewed for further clues to a possible disturbance(s).
When it is clinically indicated, values for pH and Pco 2 are obtained by
blood gas determination. If the evidence up to this point indicates the
presence of at least one disturbance, the data are examined to see if
compensation for this disturbance is appropriate. If not, a mixed disturbance
must be present. A normal pH in the setting of an abnormal serum HC0 3 -
concentration or Pco 2 also suggests a mixed disturbance since compensation
rarely corrects the pH back to normal. Of course, a pH deviated in the
opposite direction than that expected' for a known primary disturbance makes
the diagnosis of a mixed disturbance certain.
The diagnosis of a mixed acid-base disturbance is therefore based on an
analysis of all the clinical data and not just the blood gas measurements.
Treatment of the disorders should be directed at maintaining a normal or near
normal pH. Some combined acid-base disorders are important to recognize
because they can result in a severe deviation in blood pH that demands
immediate, specific therapy. Other mixed disturbances result in a pH which is
near normal but are important to recognize since they can alert the clinician to
the possibility of certain clinical derangements such as septic shock or drug
ingestion. Careful analysis of mixed acid-base disturbances in this way is not
difficult and can provide the clinician with important diagnostic and thera-
peutic information to be used in caring for his (her) patients.
ACKNOWLEDGMENT
We are indebted to Dr. John Forrest for his helpful comments and sug-
gestions.
360 MARGARET BIA AND SAMUEL O. THIER
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